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Non-steroidal anti-inflammatory drugs (NSAIDs) are crucial components of multimodal analgesia for musculoskeletal injuries, targeting cyclooxygenase (COX) enzymes (COX-1 and/or COX-2 isoenzymes). Concerns exist regarding their potential interference with bone healing and orthopaedic device-related infections (ODRI), where data are limited. This study aimed to investigate whether the COX-selectivity of NSAIDs interfered with antibiotic efficacy and bone changes in the setting of an ODRI. In vitro testing demonstrated that combining celecoxib (a COX-2 inhibitor) with cefazolin significantly enhanced antibacterial efficacy compared to cefazolin alone (p < 0.0001). In vivo experiments were performed using Staphylococcus epidermidis in the rat proximal tibia of an ODRI model. Long and short durations of celecoxib treatment in combination with antibiotics were compared to a control group receiving an antibiotic only. The long celecoxib treatment group showed impaired infection clearance, while the short celecoxib treatment showed increased bone formation (day 6, p < 0.0001), lower bone resorption (day 6, p < 0.0001), and lower osteolysis (day 6, BV/TV: p < 0.0001; BIC: p = 0.0005) compared to the control group, without impairing antibiotic efficacy (p > 0.9999). Given the use of NSAIDs as part of multimodal analgesia, and considering these findings, short-term use of COX-2 selective NSAIDs like celecoxib not only aids pain management but also promotes favorable bone changes during ODRI. [ABSTRACT FROM AUTHOR]

Background: Osteochondral allograft transplantation (OCAT) and meniscus allograft transplantation (MAT) have each become more commonly implemented for the treatment of young to middle-aged patients with complex knee pathology. Evidence regarding tibiofemoral OCAT in the setting of concurrent MAT is limited. Hypothesis/Purpose: The purpose of this study was to characterize outcomes for femoral condyle OCAT with concurrent MAT (OCAT+MAT) in the ipsilateral compartment of patients after evidence-based shifts in practice. It was hypothesized that OCAT+MAT would be associated with successful outcomes characterized by statistically significant and clinically meaningful improvements in patient-reported outcome measures (PROMs) of knee pain and function in >80% of patients for at least 2 years after transplantation. Study Design: Case series; Level of evidence, 4. Methods: With institutional review board approval and documented informed consent, patients who underwent primary OCAT+MAT between 2016 and 2020 and enrolled in a lifelong registry for prospective collection of outcomes after OCAT were included. Patients with minimum 2-year follow-up data regarding complications, failures, adherence, and PROMs were analyzed. Patients who required OCAT and/or MAT revision or conversion to arthroplasty were defined as experiencing treatment failures. Results: A total of 23 consecutive patients (mean age, 37.1 years; mean body mass index, 28 kg/m2; 14 men) met the inclusion criteria, with a mean follow-up of 51 months (range, 24-86 months). The initial treatment success rate was 78% based on 5 initial treatment failures, and the overall success rate was 83% based on a successful revision OCAT. All failures occurred in the medial compartment. Older patient age (42.2 vs 32.1 years; P =.046) and nonadherence to postoperative restriction and rehabilitation protocols (P =.033; odds ratio, 14) were significant risk factors for treatment failure. All measured PROMs achieved significant improvements (P <.001) and minimum clinically important differences at a minimum of 2 years postoperatively. Conclusion: OCAT+MAT was associated with successful short- to mid-term outcomes in 83% of cases. Evidence-based shifts in practice were implemented before the enrollment of this patient cohort. Older patients and those who were not adherent to postoperative restriction and rehabilitation protocols had a significantly higher risk for treatment failure and subsequent conversion to arthroplasty. [ABSTRACT FROM AUTHOR]

Aims Among individuals with alcohol use disorder (AUD), sleep disturbances are pervasive and contribute to the etiology and maintenance of AUD. However, despite increased attention toward the relationship between alcohol use and sleep, limited empirical research has systematically examined whether reductions in drinking during treatment for AUD are associated with improvements in sleep problems. Methods We used data from a multisite, randomized, controlled trial that compared 6 months of treatment with gabapentin enacarbil extended-release with placebo for adults with moderate-to-severe AUD (N  = 346). The Timeline Follow-back was used to assess WHO risk drinking level reductions and the Pittsburgh Sleep Quality Index was used to assess sleep quality over the prior month at baseline and the end of treatment. Results Sleep problem scores in the active medication and placebo groups improved equally. Fewer sleep problems were noted among individuals who achieved at least a 1-level reduction (B  = −0.99, 95% confidence interval (CI) [−1.77, −0.20], P  = .014) or at least a 2-level reduction (B  = −0.80, 95% CI [−1.47, −0.14], P  = .018) in WHO risk drinking levels at the end of treatment. Reductions in drinking, with abstainers excluded from the analysis, also predicted fewer sleep problems at the end of treatment (1-level: B  = −1.01, 95% CI [−1.83, −0.20], P  = .015; 2-level: B  = −0.90, 95% CI [−1.59, −0.22], P  = .010). Conclusions Drinking reductions, including those short of abstinence, are associated with improvements in sleep problems during treatment for AUD. Additional assessment of the causal relationships between harm-reduction approaches to AUD and improvements in sleep is warranted. [ABSTRACT FROM AUTHOR]

Introduction: Cryoablation therapy for pulmonary vein isolation (PVI) to treat paroxysmal atrial fibrillation (PAF) is well established. A novel 28 mm cryoballoon system designed to operate under low pressure to safely reach a lower nadir temperature and maintain constant balloon size during cooling has not been prospectively studied in a large patient population for safety and efficacy. The FROZEN AF (NCT04133168) trial was an international multicenter, open‐label, prospective, single‐arm study on the safety and performance of a novel cryoballoon system for treatment of PAF. Methods and Results: The study enrolled patients at 44 sites in 10 countries across North America, Europe, and Asia. Subjects were indicated for PVI treatment of PAF and had failed or were intolerant of one or more antiarrhythmic drugs. Procedural outcomes were defined based on the 2017 HRS consensus statement. Follow‐up was performed at 7 days, 3, 6, and 12 months. Data are reported as mean ± SD or median (IQR). PVI was performed with a 28 mm cryoballoon in 325 drug refractory PAF patients. Complete PVI was achieved in 95.7% of patients. In cryoablation lesions longer than 60 s, 60.1% of PV isolations required only a single cryoballoon application. Procedure related complications included: phrenic nerve palsy [temporary 4 (1.2%), persistent 0 (0.0%)], cardiac tamponade/perforation 2 (0.6%), and air embolism 1 (0.3%). Freedom from documented atrial arrhythmia recurrence at 12 months was 79.9% (AF 82.7%, AFL 96.5%, AT 98.1%), antiarrhythmic drugs (AAD) were continued or re‐initiated in 26.8% of patients after the 3‐month blanking period. Additionally, an extension arm enrolled 50 pts for treatment with 28/31 mm variable size cryoballoon. A single temporary PNP occurred in this group, which resolved before discharge. Freedom from documented recurrence at 12 months in these pts was 82.0%. Conclusions: This novel cryoballoon may facilitate PVI to treat PAF, providing more options to address the variety of anatomies present in patients with PAF. This cryoballoon system proved to be safe and effective for treatment of patients with drug refractory or drug intolerant PAF. [ABSTRACT FROM AUTHOR]

Background: Ulcerative colitis (UC) is a relapsing–remitting inflammatory condition that has an increasing incidence across the world, including in the Middle East. Biological monoclonal antibody drugs (biologics) have been shown to be advantageous in treating UC. We undertook a review of the currently available biological and small-molecule therapies, with a particular emphasis on those currently licensed in the United Arab Emirates (UAE). Methods: We conducted a literature search for studies on biological therapies using the PubMed, MEDLINE, and Embase databases using a list of keywords that were generated following referral to existing treatment guidelines for UC. Papers looking at biological and small-molecule treatments for UC in adult populations were included. Pediatric, pregnancy, and cost-effectiveness studies were excluded. Results and Discussion: There are currently three classes of biologics (anti-tumor necrosis factors (anti-TNFs), anti-integrins, and anti-interleukins) and one class of small-molecule therapy (Janus kinase (JAK) inhibitor) licensed for UC treatment in the UAE. Within the anti-TNF class, three medications have been approved: infliximab, adalimumab, and golimumab. For JAK inhibitors, there are two: tofacitinib and upadacitinib. There is only one licensed medication in the remaining classes: vedolizumab (anti-integrin) and ustekinumab (anti-interleukin). The length of studies varied from 6–8 weeks for induction studies and 52 weeks for maintenance studies. The studies demonstrated increased efficacy in these medications compared to placebos when clinical response, clinical remission, and other secondary measures such as mucosal healing were assessed following the induction and maintenance phases. Biosimilars of infliximab and adalimumab are also available for treating UC, and their safety and efficacy were compared to their biologic originators. Conclusions: The introduction of biologics has been proven to be beneficial for the treatment of UC. This review summarizes the efficacy and safety of each biological class in the treatment of the disease; however, biological drug registries and further studies are required to offer more insight into the comparative efficacy and safety of these agents. [ABSTRACT FROM AUTHOR]

Introduction: When considering treatment options for geriatric patients with lower extremity fractures, little is known about which outcomes are prioritized by patients. This study aimed to determine the patient preferences for outcomes after a geriatric lower extremity fracture. Materials and Methods: We administered a discrete choice experiment survey to 150 patients who were at least 60 years of age and treated for a lower extremity fracture at a Level I trauma center. The discrete choice experiment presented study participants with 8 sets of hypothetical outcome comparisons, including joint preservation (yes or no), risk of reoperation at 6 months and 24 months, postoperative weightbearing status, disposition, and function as measured by return to baseline walking distance. We estimated the relative importance of these potential outcomes using multinomial logit modeling. Results: The strongest patient preference was for maintained function after treatment (59%, P <.001), followed by reoperation within 6 months (12%, P <.001). Although patients generally favored joint preservation, patients were willing to change their preference in favor of joint replacement if it increased function (walking distance) by 13% (SE, 66%). Reducing the short-term reoperation risk (12%, P <.001) was more important to patients than reducing long-term reoperation risk (4%, P =.33). Disposition and weightbearing status were lesser priorities to patients (9%, P <.001 and 7%, P <.001, respectively). Discussion: After a lower extremity fracture, geriatric patients prioritized maintained walking function. Avoiding short-term reoperation was more important than avoiding long-term reoperation. Joint preservation through fracture fixation was the preferred treatment of geriatric patients unless arthroplasty or arthrodesis provides a meaningful functional benefit. Hospital disposition and postoperative weightbearing status were less important to patients than the other included outcomes. Conclusions: Geriatric patients strongly prioritize function over other outcomes after a lower extremity fracture. [ABSTRACT FROM AUTHOR]

Background: Tightly connected symptom networks have previously been linked to treatment resistance, but most findings come from small-sample studies comparing single responder v. non-responder networks. We aimed to estimate the association between baseline network connectivity and treatment response in a large sample and benchmark its prognostic value against baseline symptom severity and variance. Methods: N = 40 518 patients receiving treatment for depression in routine care in England from 2015–2020 were analysed. Cross-sectional networks were constructed using the Patient Health Questionnaire-9 (PHQ-9) for responders and non-responders (N = 20 259 each). To conduct parametric tests investigating the contribution of PHQ-9 sum score mean and variance to connectivity differences, networks were constructed for 160 independent subsamples of responders and non-responders (80 each, n = 250 per sample). Results: The baseline non-responder network was more connected than responders (3.15 v. 2.70, S = 0.44, p < 0.001), but effects were small, requiring n = 750 per group to have 85% power. Parametric analyses revealed baseline network connectivity, PHQ-9 sum score mean, and PHQ-9 sum score variance were correlated (r = 0.20–0.58, all p < 0.001). Both PHQ-9 sum score mean (β = −1.79, s.e. = 0.07, p < 0.001), and PHQ-9 sum score variance (β = −1.67, s.e. = 0.09, p < 0.001) had larger effect sizes for predicting response than connectivity (β = −1.35, s.e. = 0.12, p < 0.001). The association between connectivity and response disappeared when PHQ-9 sum score variance was accounted for (β = −0.28, s.e. = 0.19, p = 0.14). We replicated these results in patients completing longer treatment (8–12 weeks, N = 22 952) and using anxiety symptom networks (N = 70 620). Conclusions: The association between baseline network connectivity and treatment response may be largely due to differences in baseline score variance. [ABSTRACT FROM AUTHOR]

With increasing waiting lists across the UK for oral surgery under general anaesthesia (GA), inhalation sedation (IS) may provide the answer for patients to be treated more quickly. The authors believe it is an underused technique for the management of anxious and medically compromised patients requiring oral surgery. This article demonstrates, with patient examples, how IS can be used effectively. [ABSTRACT FROM AUTHOR]

In treating depression and anxiety, just over half of all clients respond. Monitoring and obtaining early client feedback can allow for rapidly adapted treatment delivery and improve outcomes. This study seeks to develop a state-of-the-art deep-learning framework for predicting clinical outcomes in internet-delivered Cognitive Behavioural Therapy (iCBT) by leveraging large-scale, high-dimensional time-series data of client-reported mental health symptoms and platform interaction data. We use de-identified data from 45,876 clients on SilverCloud Health, a digital platform for the psychological treatment of depression and anxiety. We train deep recurrent neural network (RNN) models to predict whether a client will show reliable improvement by the end of treatment using clinical measures, interaction data with the iCBT program, or both. Outcomes are based on total improvement in symptoms of depression (Patient Health Questionnaire-9, PHQ-9) and anxiety (Generalized Anxiety Disorder-7, GAD-7), as reported within the iCBT program. Using internal and external datasets, we compare the proposed models against several benchmarks and rigorously evaluate them according to their predictive accuracy, sensitivity, specificity and AUROC over treatment. Our proposed RNN models consistently predict reliable improvement in PHQ-9 and GAD-7, using past clinical measures alone, with above 87% accuracy and 0.89 AUROC after three or more review periods, outperforming all benchmark models. Additional evaluations demonstrate the robustness of the achieved models across (i) different health services; (ii) geographic locations; (iii) iCBT programs, and (iv) client severity subgroups. Results demonstrate the robust performance of dynamic prediction models that can yield clinically helpful prognostic information ready for implementation within iCBT systems to support timely decision-making and treatment adjustments by iCBT clinical supporters towards improved client outcomes. [ABSTRACT FROM AUTHOR]

Objectives Glucocorticoids (GCs) ('steroids') are used to treat rheumatic diseases but adverse effects are common. We aimed to explore the impact of GC therapy on health-related quality of life (HRQoL), to inform the development of a treatment-specific patient-reported outcome measure (PROM) for use in clinical trials and practice. Methods Semi-structured qualitative interviews were conducted with patients from the UK, USA and Australia, treated for a rheumatic condition with GCs in the last 2 years. Purposive sampling was used to select participants with a range of demographic and disease features. An initial conceptual framework informed interview prompts and cues. Interviews elicited GC-related physical and psychological symptoms and salient aspects of HRQoL in relation to GC therapy. Interview data were analysed inductively to develop initial individual themes and domains. Candidate questionnaire items were developed and refined. Results Sixty semi-structured qualitative interviews were conducted (UK n  = 34, USA n  = 10, Australia n  = 16). The mean age was 58 years; 39/60 were female; and 18 rheumatic diseases were represented. Some 126 individual themes were identified and organized into six domains: physical symptoms; psychological symptoms; psychological impact of steroids; impact of steroids on participation; impact of steroids on relationships; and benefits of steroids. Candidate questionnaire items were tested and refined by piloting with patient research partners, iterative rounds of cognitive interviews and linguistic translatability assessment, informing a draft questionnaire. Conclusion We describe an international qualitative study to develop candidate items for a treatment-specific PROM for patients with rheumatic diseases. A future survey will enable the validation of a final version of the PROM. [ABSTRACT FROM AUTHOR]

Background: In recent years, exponential growth in digital innovations and internet access has provided opportunities to deliver health services at a much greater scale than previously possible. Evidence-based technology-enabled interventions can provide cost-effective, accessible, and resource-efficient solutions for addressing mental health issues. This study evaluated the first year of a supported digital cognitive behavioral therapy (CBT) service provided by the national health service in Ireland, which has been accessible to individuals who receive a referral from one of five referring groups: General Practitioners, Primary Care Psychology, Counselling Primary Care, Community Mental Health, and Jigsaw (a nationwide youth mental health service). Methods: A retrospective, observational study examining data from the service between April 2021 to April 2022 was conducted. Descriptive statistics on referrals, account activations, user demographics, program usage, and user satisfaction were extracted, and pre-to-post clinical outcomes for depression measured by the Patient Health Questionnaire-9 and for anxiety measured by the Generalised Anxiety Disorder-7 were analysed using linear mixed effect models. Results: There were 5,298 referrals and 3,236 (61%) account activations within the year. Most users were female (72.9%) and aged between 18 and 44 years (75.4%). The CBT programs were associated with significant reductions in both depression (β = 3.34, 95% CI [3.03, 3.65], p < 0.001) and anxiety (β = 3.64, 95% CI [3.36, 3.93], p < 0.001), with large effect sizes (Cohen's d > 0.8). Time spent using the programs was also found to be a predictor of the variability in these clinical outcomes (p < 0.001), and accounting for this resulted in significantly better model fits (p < 0.001). User satisfaction ratings were also very high, exceeding 94%. Conclusions: Efforts to improve the representation of male and older adult users are warranted. However, overall, the results demonstrate how digital CBT can be provided at scale and lead to symptom reductions with large effect sizes for patients seeking help for depression and anxiety. The findings substantiate the continued use and expansion of this service in Ireland and the more widespread implementation of similar services in other international public healthcare settings. [ABSTRACT FROM AUTHOR]

Introduction: Prehospital evidence-based guidelines (EBGs) are developed to optimize clinical outcomes for emergency medical services (EMS) patients. However, widespread implementation of EBGs is often inconsistent. Therefore, this study aimed to assess the baseline knowledge and practices of EMS leaders related to EBG implementation. Methods: This was a qualitative study using focus groups to assess prehospital implementation awareness and knowledge. Participants were EMS EBG authors, EMS medical directors, and EMS professional organization leaders. Focus groups were held via video conference, audio recorded, and transcribed. Thematic coding used domains and constructs of the Consolidated Framework for Implementation Research (CFIR). Results: Six focus groups were conducted with a total of 18 participants. A total of 1,044 codes were analyzed. "Process" was the CFIR domain with the most codes (n = 350, 33.5%), followed by the "inner setting" (the EMS agency; n = 250, 23.9%), "characteristics of the intervention" (n = 203, 19.4%), "outer setting" (the health care system and community the EMS agency serves, and the broader national EMS professional context; n = 141, 13.5%), and "characteristics of individuals" (n = 100, 9.6%). The ten most frequent constructs across all domains were: reflecting and evaluating, executing, cosmopolitanism, planning, external policy and incentives, design quality and packaging, learning climate, culture, complexity, and other personal attributes. Conclusion: EMS leadership and stakeholder views on EBG implementation identified dominant themes related to the process of implementation and the culture and learning/implementation climate of EMS agencies. Opinions were mixed on the utility of the CFIR as a potential guide for EMS implementation. Further work is required to gain the frontline EMS clinician perspective on implementation and tie key themes to quantitative prehospital implementation outcomes. [ABSTRACT FROM AUTHOR]

Objective: Osteomyelitis of the frontal bone is a rare but devastating complication of frontal sinusitis. Treatment involves aggressive surgery to remove all sequestra in combination with long-term antibiotic therapy. However, systemic antibiotics may struggle to penetrate any remaining infection in devascularised areas, and the morbidity associated with surgical resection of some areas of the skull base is too high. In contrast, locally implanted antibiotics provide a reliable, high concentration of treatment to these areas while also minimising potential systemic side effects. The clinical application of tobramycin beads has primarily been used in orthopaedics as an adjunct to the treatment of tibial osteomyelitis or prosthetic joint infection. Case report: To the best of the authors' knowledge, the two cases discussed here represent the first use of tobramycin antibiotic beads in frontal sinus osteomyelitis secondary to chronic rhinosinusitis. Conclusion: These cases show promising use of tobramycin beads in recalcitrant frontal osteomyelitis. [ABSTRACT FROM AUTHOR]

Patients with acute ischemic stroke (AIS) eligible for thrombolysis benefit when thrombolysis is administered quickly, and mobile stroke units (MSU) can facilitate timely thrombolysis. We sought to compare time metrics and clinical outcomes of AIS patients receiving thrombolysis in an MSU compared with patients arriving via local emergency medical services (EMS). We performed a retrospective, non-randomized, cohort study comparing MSU-arriving to EMS-arriving AIS patients from January 20, 2017 through November 30, 2020. The primary outcome was rate of return to baseline functional status as measured by the modified Rankin Score (mRS) 90 days after thrombolysis. Secondary outcomes included evaluation and treatment intervals from last known well, treatment rate in the first hour of symptoms, hospital length of stay, and mortality. Chi square and Student's t-test were used to compare groups. Of 1752 total patients with prehospital suspected stroke, 975 (55.7%) were transported via MSU, of whom 431 (44.2%) were diagnosed with stroke, including 368 (85.4%) with AIS, and 69 AIS patients (18.8%) received thrombolysis. Of 777 (44.3%) EMS-arriving patients, 373 (48%) were diagnosed with stroke, including 305 (81.8%) with AIS, and 74 (24.3%) received thrombolysis. Though not statistically significant, point estimates of the proportion of AIS patients treated with thrombolysis returning to baseline functional status were more commonly observed for MSU than for EMS transports when the baseline mRS was 0-2 (45.8% vs 33.3%), 0-3 (41.9% vs 33.3%), and 4-5 (71.4% vs 20.0%). MSU patients were more likely to receive thrombolysis in the first 60 minutes of symptom onset (31.9% vs 12.2%, p = 0.006). Overall mortality rates regardless of baseline mRS were similar between groups. AIS patients received thrombolysis faster in the MSU compared with EMS and more frequently within 60 minutes of stroke onset. Point estimates for 90-day clinical outcomes of AIS patients treated with thrombolysis favored MSU without a statistically significant difference. [ABSTRACT FROM AUTHOR]

Background: Depression is an important, potentially modifiable dementia risk factor. However, it is not known whether effective treatment of depression through psychological therapies is associated with reduced dementia incidence. The aim of this study was to investigate associations between reduction in depressive symptoms following psychological therapy and the subsequent incidence of dementia. Methods: National psychological therapy data were linked with hospital records of dementia diagnosis for 119808 people aged 65+. Participants received a course of psychological therapy treatment in Improving Access to Psychological Therapies (IAPT) services between 2012 and 2019. Cox proportional hazards models were run to test associations between improvement in depression following psychological therapy and incidence of dementia diagnosis up to eight years later. Results: Improvements in depression following treatment were associated with reduced rates of dementia diagnosis up to 8 years later (HR = 0.88, 95% CI 0.83–0.94), after adjustment for key covariates. Strongest effects were observed for vascular dementia (HR = 0.86, 95% CI 0.77–0.97) compared with Alzheimer's disease (HR = 0.91, 95% CI 0.83–1.00). Conclusions: Reliable improvement in depression across psychological therapy was associated with reduced incidence of future dementia. Results are consistent with at least two possibilities. Firstly, psychological interventions to improve symptoms of depression may have the potential to contribute to dementia risk reduction efforts. Secondly, psychological therapies may be less effective in people with underlying dementia pathology or they may be more likely to drop out of therapy (reverse causality). Tackling the under-representation of older people in psychological therapies and optimizing therapy outcomes is an important goal for future research. [ABSTRACT FROM AUTHOR]

Background. There are limited data on the clinical characteristics and outcomes of patients with myasthenia gravis (MG) admitted to the intensive care unit (ICU) at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH). Objectives. The aim was to study the clinical characteristics and outcomes of patients with MG admitted to the CMJAH over two decades. Methods. A retrospective study was undertaken of patients with MG admitted to the multidisciplinary ICU of CMJAH over a 20-year period, from 1998 to 2017. Demographic data, clinical features, management and outcomes of patients were assessed and reviewed from the case records. Results. Thirty-four patients with MG were admitted to the ICU during this period: 24 female and 10 male. The mean age ± SD was 37.4 ± 13.0 years, with a range of 16 - 66 years. Four patients were human immunodeficiency virus (HIV)-positive. The mean length of stay (LOS) in ICU was 10.6 ± 20.1 days, ranging from 1 to 115 days. Two patients were diagnosed with MG in the ICU after failure to wean from the ventilator. Overall, 22 patients were intubated and ventilated on admission. Morbidities included self-extubation, aspiration pneumonia and iatrogenic pneumothorax. History of thymectomy was present in 12 patients. The treatments received for MG included pyridostigmine (73.5%), corticosteroids (55.9%), azathioprine (35.3%), plasmapheresis (26.5%) and intravenous immunoglobulin (8.8%). The overall mortality in the ICU was 5.9%. Conclusion. MG is a serious disorder with considerable morbidity and mortality. It is, however, a potentially manageable disease, provided that appropriate ICU resources are available. [ABSTRACT FROM AUTHOR]

Low‐intensity interventions for common mental disorders (CMD) address issues such as clinician shortages and barriers to accessing care. However, there is a lack of research into their comparative effectiveness in routine care. We aimed to compare treatment effects of three such interventions, utilizing four years' worth of routine clinical data. Users completing a course of guided self‐help bibliotherapy (GSH), internet‐delivered cognitive behavioural therapy (iCBT) or psychoeducational group therapy (PGT) from a stepped‐care service within the NHS in England were included. Propensity score models (stratification and weighting) were used to control for allocation bias and determine average treatment effect (ATE) between the interventions. 21,215 users comprised the study sample (GSH = 12,896, iCBT = 6862, PGT = 1457). Adherence‐to‐treatment rates were higher in iCBT. All interventions showed significant improvements in depression (PHQ‐9), anxiety (GAD‐7) and functioning (WSAS) scores, with largest effect sizes for iCBT. Both propensity score models showed a significant ATE in favour of iCBT versus GSH and PGT, and in favour of GSH versus PGT. Discernible differences in effectiveness were seen for iCBT in comparison with GSH and PGT. Given variance in delivery mode and human resources between different low‐intensity interventions, building on these findings would be valuable for future service provision and policy decision making. [ABSTRACT FROM AUTHOR]

Background: Micronutrients have been associated with disease severity and poorer clinical outcomes in patients with COVID-19. However, there is a paucity of studies examining if the relationship with micronutrient status and clinical outcomes is independent of recognised prognostic factors, specifically frailty and the systemic inflammatory response (SIR). The aim of the present study was to examine the relationship between micronutrient status, frailty, systemic inflammation, and clinical outcomes in patients admitted with COVID-19. Methods: Retrospective analysis of prospectively collected data was performed on patients with confirmed COVID-19, admitted to hospital between the 1st April 2020–6th July 2020. Clinicopathological characteristics, frailty assessment, biochemical and micronutrient laboratory results were recorded. Frailty status was determined using the Clinical Frailty scale. SIR was determined using serum CRP. Clinical outcomes of interest were oxygen requirement, ITU admission and 30-day mortality. Categorical variables were analysed using chi-square test and binary logistics regression analysis. Continuous variables were analysed using the Mann–Whitney U or Kruskal Wallis tests. Results: 281 patients were included. 55% (n = 155) were aged ≥ 70 years and 39% (n = 109) were male. 49% (n = 138) of patients were frail (CFS > 3). 86% (n = 242) of patients had a serum CRP > 10 mg/L. On univariate analysis, frailty was significantly associated with thirty-day mortality (p < 0.001). On univariate analysis, serum CRP was found to be significantly associated with an oxygen requirement on admission in non-frail patients (p = 0.004). Over a third (36%) of non-frail patients had a low vitamin B1, despite having normal reference range values of red cell B2, B6 and selenium. Furthermore, serum CRP was found to be significantly associated with a lower median red cell vitamin B1 (p = 0.029). Conclusion: Vitamin B1 stores may be depleted in COVID-19 patients experiencing a significant SIR and providing rationale for thiamine supplementation. Further longitudinal studies are warranted to delineate the trend in thiamine status following COVID-19. [ABSTRACT FROM AUTHOR]

Introduction: Pulmonary vein isolation (PVI) is well established as a primary treatment for atrial fibrillation (AF). The POLAR ICE study was designed to collect prospective real world data on the safety and effectiveness of the POLARxTM cryoballoon for PVI to treat paroxysmal AF. Methods: POLAR ICE, a prospective, non‐randomized, multicenter (international) registry (NCT04250714), enrolled 399 patients across 19 European centers. Procedural characteristics, such as time to isolation, cryoablations per pulmonary vein (PV), balloon nadir temperature, and occlusion grade were recorded. PVI was confirmed with entrance block testing. Results: Data on 372 de novo PVI procedures (n = 2190 ablations) were collected. Complete PVI was achieved in 96.8% of PVs. Procedure and fluoroscopy times were 68.2 ± 24.6 and 15.6 ± 9.6 min, respectively. Left atrial dwell time was 46.6 ± 18.3 min. Grade 3 or 4 occlusion was achieved in 98.2% of PVs reported and 71.2% of PVs isolation required only a single cryoablation. Of 2190 cryoapplications, 83% had a duration of at least 120 s; nadir temperature of these ablations averaged −56.3 ± 6.5°C. There were 6 phrenic nerve palsy events, 2 of which resolved within 3 months of the procedure. Conclusion: This real‐world usage data on a novel cryoballoon suggests this device is effective, safe, and relatively fast in centers with cryoballoon experience. These data are comparable to prior POLARx reports and in keeping with reported data on other cryoballoons. Future studies should examine the long‐term outcomes and the relationship between biophysical parameters and outcomes for this novel cryoballoon. [ABSTRACT FROM AUTHOR]

Aim: First Episode Rapid Early Intervention for Eating Disorders (FREED) is an early intervention model for young people with recent‐onset eating disorders (ED). Promising results from a previous single‐centre study and a four‐centre study (FREED‐Up) have led to the rapid national scaling of FREED to ED services in England (FREED‐4‐All). Our aim was to evaluate duration of an untreated ED (DUED), wait time target adherence, and clinical outcomes in FREED‐4‐All and compare these to the (benchmark) findings of the earlier FREED‐Up study. Method: FREED services submit de‐identified data to the central FREED team quarterly. The current study covers the period between September 2018 and September 2021. This FREED‐4‐All dataset includes 2473 patients. These were compared to 278 patients from the FREED‐Up study. Results: DUED was substantially shorter in the FREED‐4‐All dataset relative to the FREED‐Up study (15 vs. 18 months). Adherence to the wait time targets was comparable in both cohorts (~85% of engagement calls attempted in <2 days, ~50%–60% of assessments offered in <14 days, ~40% of treatment offered in <28 days). Patients in the FREED‐4‐All dataset experienced significant improvements in ED and general psychological symptoms from pre‐ to post‐treatment that were comparable to the FREED‐Up study. These findings should be interpreted cautiously as only 6% of FREED‐4‐All patients had post‐treatment data. Conclusions: Data from the FREED‐4‐All evaluation suggest that FREED is replicating at scale. However, these data are flawed, uncertain, proximate, and sparse and should therefore be used carefully alongside other evidence and clinical experience to inform decision making. [ABSTRACT FROM AUTHOR]

Background Artemether-lumefantrine (AL) is the most widely used artemisinin-based combination therapy in Sub-Saharan Africa and is threatened by the emergence of artemisinin resistance. Dosing is suboptimal in young children. We hypothesized that extending AL duration will improve exposure and reduce reinfection risks. Methods We conducted a prospective, randomized, open-label pharmacokinetic/pharmacodynamic study of extended duration AL in children with malaria in high-transmission rural Uganda. Children received 3-day (standard 6-dose) or 5-day (10-dose) AL with sampling for artemether, dihydroartemisinin, and lumefantrine over 42-day clinical follow-up. Primary outcomes were (1) comparative pharmacokinetic parameters between regimens and (2) recurrent parasitemia analyzed as intention-to-treat. Results A total of 177 children aged 16 months to 16 years were randomized, contributing 227 total episodes. Terminal median lumefantrine concentrations were significantly increased in the 5-day versus 3-day regimen on days 7, 14, and 21 (P <.001). A predefined day 7 lumefantrine threshold of 280 ng/mL was strongly predictive of recurrence risk at 28 and 42 days (P <.001). Kaplan–Meier estimated 28-day (51% vs 40%) and 42-day risk (75% vs 68%) did not significantly differ between 3- and 5-day regimens. No significant toxicity was seen with the extended regimen. Conclusions Extending the duration of AL was safe and significantly enhanced overall drug exposure in young children but did not lead to significant reductions in recurrent parasitemia risk in our high-transmission setting. However, day 7 levels were strongly predictive of recurrent parasitemia risk, and those in the lowest weight-band were at higher risk of underdosing with the standard 3-day regimen. Clinical Trial Registration ClinicalTrials.gov number NCT03453840. [ABSTRACT FROM AUTHOR]

Background: Clients independently applying Cognitive Behavior Therapy (CBT) skills is an important outcome of CBT‐based treatments. The relationship between posttherapeutic CBT skills usage and clinical outcomes remains under‐researched—especially after internet‐delivered CBT (iCBT). Objective: Explore contemporaneous and lagged effects of posttherapeutic CBT skills usage frequency on iCBT follow‐up outcomes. Method: Nested within a randomized controlled trial, 241 participants received 8‐week supported iCBT for anxiety and/or depression, completing measures of anxiety, depression, functional impairment, and CBT skills usage frequency at 3‐, 6‐, 9‐, and 12‐month follow‐up. Cross‐lagged panel models evaluated primary aims. Results: While analyses support a contemporaneous relationship between anxiety, depression, functional impairment, and CBT skills usage frequency, no consistent lagged effects were observed. Conclusion: Findings align with qualitative research but the role of CBT skills usage in the maintenance of iCBT effects remains unclear. Innovative research modeling temporal and possibly circular relationships between CBT skill usage and clinical outcomes is needed to inform iCBT optimization. Key Practitioner Message: The independent application of Cognitive Behavior Therapy (CBT) skills by clients is an important outcome of all CBT‐based interventions and may contribute to how clinical effects are maintained into follow‐up.In this study, participants who reported more frequent use of CBT skills also showed lower symptoms of depression and anxiety and less functional impairment after internet‐delivered CBT had ended.However, questions over causal links between posttherapeutic CBT skills usage and clinical outcomes prevail and more robust research is needed to draw firm conclusions. [ABSTRACT FROM AUTHOR]

Objectives: Discussions regarding the specific management and outcomes for laryngeal MEC are limited to very small, single-institution case series. To look further into the diagnosis and management of these uncommon non-squamous cell carcinomas of the larynx, we present 3 recent cases of laryngeal MEC treated at our institution. Methods: Patients at a tertiary hospital treated for MEC between October 2019 and December 2020 were retrospectively identified. Chart review, imaging analysis, and histologic slide creation were completed for all patients. Results: We identified and treated 2 patients with high-grade supraglottic and 1 patient with intermediate-grade glottic MEC. These patients presented to our clinic with a primary complaint of either gradual, worsening dysphonia, dysphagia, or both. All patients underwent laryngovideostroboscopy as well as panendoscopy with directed submucosal biopsy, which was consistent with MEC. MRI was performed in 2 of the cases further elucidating the extent of submucosal spread. PET-CT was performed in all 3 cases, and none demonstrated evidence of regional or distal metastases. Surgically, high-grade MEC lesions were treated with a total laryngectomy. The intermediate MEC lesion was managed with a supracricoid partial laryngectomy (SCPL). Surgical margins were free of tumor in all cases with no nodal metastases by modified radical neck dissection. Radiation therapy was offered to both high-grade MEC patients and declined by one. Radiation was not recommended to the patient with intermediate-grade MEC as we believed that the risk of additional treatment outweighed the benefit. Conclusion: We believe that MEC of the larynx should be considered in patients with atypical submucosal laryngeal masses. Laryngovideostroboscopy, MRI, and PET imaging may be valuable in determining the extent of the lesions and planning appropriate surgery. Postoperative radiation therapy should be considered a per tumor grade in other more studied sites, as there is no data on efficacy in laryngeal MEC. [ABSTRACT FROM AUTHOR]

Accurate glenoid component positioning during total shoulder arthroplasty (TSA) is critical for prosthesis longevity and postoperative function. Glenoid component positioning in many TSA procedures depends on the insertion of a guide pin through the glenoid vault. However, up to 48% of TSA procedures involve guide pin malpositioning. The aim of this study was to evaluate the ability of a novel structured light imaging system to visualize glenoid guide pin position and trajectory in surgically exposed cadaveric shoulders. Computed tomography (CT)-based and magnetic resonance imaging (MRI)-based workflows and subchondral bone–based and glenoid cartilage–based workflows were compared. Preoperative cone-beam CT (CBCT) and MRI images were acquired for 5 intact cadaveric shoulders. Following deltopectoral surgical exposure, a glenoid vault guide pin was inserted through the glenoid vault of each scapula as in a clinical TSA procedure. A 3D printed optical tracker was placed over the guide pin, and a 3D optical surface image of the glenoid and tracker was acquired using a handheld structured light sensor. A postprocedural CBCT was acquired for each shoulder to verify guide pin position and trajectory. The imaging procedure was repeated after débridement of the glenoid cartilage to expose subchondral bone. The guide pin was segmented from the postprocedural CBCT image (actual guide pin). A virtual model of the tracker was aligned with a co-linear representation of the intraoperative guide pin (predicted guide pin). A series of image registrations aligned the actual and predicted guide pin positions to yield visualization accuracy, defined as the trajectory and offset errors between predicted and actual guide pins. The mean guide pin trajectory and offset errors based on the subchondral bone were 2.22 ± 1.27° and 1.27 ± 0.46 mm for the CT-based workflow and 2.27 ± 1.72° and 1.78 ± 0.92 mm for the MRI-based workflow, respectively. Registration of the cartilage surface models visualized in the MRI images reduced accuracy to a trajectory error of 3.89 ± 1.57° (P =.147) and offset error of 2.28 ± 1.33 mm (P =.217). The Bullseye structured light imaging system presented an accurate approach for glenoid guide pin verification and adjustment during TSA using preoperative MRI or CT. Future development for the implementation of the Bullseye system should focus on improving surface segmentations and automation of the computer vision algorithm needed to facilitate clinical translation. [ABSTRACT FROM AUTHOR]

The origins of mindfulness go back some 25 centuries to Eastern teachings, including Buddhism and Hinduism. Mindfulness-based interventions gained credence in Western mental health settings in the late 1970s through the work of medical researcher Kabat-Zinn, whose interest in Eastern meditation led him to develop a program for stress reduction. Since then, mindfulness-based interventions have been utilized for various populations, including older people with anxiety. Group mindfulness-based interventions have demonstrated benefits for older people with anxiety living in residential aged care and the community. In primary care settings, innovative delivery models for group mindfulness-based interventions could be facilitated by nurses to support older people with anxiety to age in place with dignity. The benefits of mindfulness-based interventions suggest the value of integrating ancient Eastern techniques with modern Western strategies to achieve better health outcomes for older people with mental health concerns. [ABSTRACT FROM AUTHOR]

Voice tremor is a common, yet debilitating symptom for patients suffering from a number of tremor-associated disorders. The key to targeting effective treatments for voice tremor requires a fundamental understanding of the pathophysiology that underpins the tremor mechanism and accurate identification of the disease in affected patients. An updated review of the literature detailing the current understanding of voice tremor (with or without essential tremor), its accurate diagnosis and targeted treatment options was conducted, with a specific focus on the role of botulinum neurotoxin. Judicious patient selection, following detailed characterisation of voice tremor qualities, is essential to optimising treatment outcomes for botulinum neurotoxin therapy, as well as other targeted therapies. Further focused investigation is required to characterise the response to targeted treatment in voice tremor patients and to guide the development of innovative treatment options. [ABSTRACT FROM AUTHOR]

Background: Compared with anaemia before surgery, the underlying pathogenesis and implications of postoperative anaemia are largely unknown.Methods: This retrospective cohort study analysed prospective data obtained from 2983 adult patients across 47 centres enrolled in a clinical trial evaluating restrictive and liberal intravenous fluids. The primary endpoint was persistent disability or death up to 90 days after surgery. Secondary endpoints included major septic complications, hospital stay, and patient quality of recovery using a 15-item quality of recovery (QoR-15) score, hospital re-admissions, and disability-free survival up to 12 months after surgery. Anaemia and disability were defined according to the WHO definitions. Multivariable regression was used to adjust for baseline risk and surgery.Results: A total of 2983 patients met inclusion criteria for this study, of which 78.5% (95% confidence interval [CI], 76.7-80.1%) had postoperative anaemia. Patients with postoperative anaemia had a higher adjusted risk of death or disability up to 90 days after surgery when compared with those without anaemia: 18.2% vs 9.2% (risk ratio [RR]=1.51; 95% CI, 1.10-2.07, P=0.011); lower QoR-15 scores on Day 3 and Day 30, 105 (95% CI, 87-119) vs 114 (95% CI, 99-128; P<0.001), and 130 (95% CI, 112-140) vs 139 (95% CI, 121-144; P<0.011), respectively; higher adjusted risk of a composite of mortality/septic complications, 2.01 (95% CI, 1.55-42.67; P<0.001); unplanned admission to ICU (RR=2.65; 95% CI, 1.65-4.23; P<0.001); and longer median (inter-quartile range [IQR]) hospital stays, 6.6 (4.4-12.4) vs 3.7 (2.5-6.5) days (P<0.001).Conclusions: Postoperative anaemia is common and is independently associated with poor outcomes after surgery. Optimal prevention and treatment strategies need to be investigated.Clinical Trial Registration: NCT04978285 (ClinicalTrials.gov). [ABSTRACT FROM AUTHOR]

Objective: To investigate post‐treatment relapse and remission rates 3, 6 and 9 months after completion of an acute phase of a clinician‐supported internet‐delivered cognitive‐behavioural therapy (iCBT) for anxiety and depressive symptoms, within a routine care setting. Method: Secondary analysis from a 12‐month pragmatic randomized‐controlled trial delivered within the Improving Access to Psychological Therapies (IAPT) programme in England. Participants in the intervention arm were included if they met criteria for reliable recovery from depression (PHQ‐9) and anxiety (GAD‐7) at post‐treatment assessment. Survival analysis was used to assess durability of treatment effects and determine predictors to relapse at 3‐, 6‐ and 9‐month follow‐up. Hazard ratios predicting time‐to‐relapse were estimated with semi‐parametric Cox proportional hazards model. Results: Of the 241 participants in the intervention arm, 89 participants met the criteria for reliable recovery from depression and anxiety at the post‐treatment assessment. Of these 89 eligible cases, 29.2% relapsed within the 9‐month period, with 70.8% remaining in remission at 9 months post‐treatment. Of those who relapsed, 53.8% experienced a relapse of depression and anxiety; 7.7% experienced a relapse of depression only; and 38.4% experienced a relapse of anxiety only. Younger age, having a long‐term condition, and residual symptoms of anxiety at end‐of‐treatment were all significant predictors of relapse. Conclusions: This study is the first to explore the remission and relapse rates after an acute phase of iCBT treatment, within a routine, stepped‐care setting. The results add to the scarce literature on the durability of the effects of iCBT treatment in routine care settings, where patients are not typically followed up after receiving a completed course of treatment. [ABSTRACT FROM AUTHOR]

Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused high inpatient mortality and morbidity throughout the world. COVID-19 convalescent plasma (CCP) has been utilized as a potential therapy for patients hospitalized with coronavirus disease 2019 (COVID-19) pneumonia. This study evaluated the outcomes of hospitalized patients with COVID-19 treated with CCP in a prospective, observational, multicenter trial. Methods From April through August 2020, hospitalized patients with COVID-19 at 16 participating hospitals in Colorado were enrolled and treated with CCP and compared with hospitalized patients with COVID-19 who were not treated with convalescent plasma. Plasma antibody levels were determined following the trial, given that antibody tests were not approved at the initiation of the trial. CCP-treated and untreated hospitalized patients with COVID-19 were matched using propensity scores followed by analysis for length of hospitalization and inpatient mortality. Results A total of 542 hospitalized patients with COVID-19 were enrolled at 16 hospitals across the region. A total of 468 hospitalized patients with COVID-19 were entered into propensity score matching with 188 patients matched for analysis in the CCP-treatment and control arms. Fine-Gray models revealed increased length of hospital stay in CCP-treated patients and no change in inpatient mortality compared with controls. In subgroup analysis of CCP-treated patients within 7 days of admission, there was no difference in length of hospitalization and inpatient mortality. Conclusions These data show that treatment of hospitalized patients with COVID-19 treated with CCP did not significantly improve patient hospitalization length of stay or inpatient mortality. [ABSTRACT FROM AUTHOR]

Local antibiotic therapy is increasingly being recognised for its role in preventing and treating orthopaedic device-related infection (ODRI). A bioresorbable, injectable gentamicin-loaded hydrogel has been developed to deliver local antibiotics at the time of surgery with potential for both prevention and treatment of ODRI. In a prophylaxis model, the antibiotic hydrogel was compared with systemic perioperative antibiotic prophylaxis alone in twelve sheep (six per group) at the time of intramedullary (IM) nail insertion to the tibia, which was inoculated with methicillin-sensitive Staphylococcus aureus (MSSA). In a treatment model of single-stage revision surgery, adjunctive antibiotic-loaded hydrogel was compared with systemic antibiotics alone in a single stage revision of MSSA infection associated with a tibia intramedullary nail in eleven sheep (five/six per group). The primary endpoint was quantitative microbiological results of soft tissue, bone and sonicate fluid from explanted hardware at the time of euthanasia. At euthanasia, the control sheep that received no local antibiotics in the prophylaxis model were all culture-positive (median 1x108, range 7x106-3x108 colony forming units, CFU) while only two of six sheep receiving local gentamicin had any culture positive biopsies (median 1x101, range 0 - 1x105 CFU). For the treatment model, sheep receiving only systemic antibiotics were all culture-positive (median 8x105, range 2x103- 9x106 CFU) while only two of six sheep treated with gentamicin-loaded hydrogel had any culture positive biopsies (median 3x102, range 0 - 7x104 CFU). Local gentamicin concentrations measured in extracellular fluid in the tibial canal show a burst release of gentamicin from the hydrogel. Serum gentamicin concentrations peaked in both models at one day post application and were below detection limit thereafter. This study has demonstrated the effective use of a locally delivered antibiotic hydrogel for both the prevention and treatment of ODRI that is superior to that of systemic antibiotics alone. Future studies will endeavour to translate from preclinical to clinical research trials. [ABSTRACT FROM AUTHOR]

Background: Engraftment syndrome (ES) is a common complication of autologous hematopoietic cell transplantation (HCT). The difference in incidence of ES between melphalan formulations has not been widely reported throughout the literature and would allow for a more comprehensive understanding of the advantages and disadvantages of both melphalan formulations. Patients and methods: This retrospective, single-center, observational study evaluated 83 adult multiple myeloma and immunoglobulin light chain amyloidosis patients who received either propylene glycol-containing (PG) or propylene glycol-free (PG-free) melphalan 140 mg/m2 as single-agent conditioning chemotherapy for autologous HCT from May 31, 2015 to May 31, 2019. The primary outcome was to assess the incidence of ES, as defined using the Maiolino criteria, with both melphalan formulations. Secondary outcomes included an analysis of potential risk factors for the development of ES, as well as an evaluation of overall length of stay (LOS). Results: The incidence of ES for PG and PG-free melphalan did not differ significantly, 14/39 (35.9%) and 12/44 (27.3%) (P = 0.4), respectively. No potential risk factors for ES were identified on multivariate logistic regression analysis. A statistically significant difference in number of days to engraftment was identified for PG and PG-free melphalan, 15.56 vs. 13.82 days (P = 0.01), respectively; although, this did not translate to a decrease in LOS, 19.9 vs. 18.59 days (P = 0.14). Conclusions: The incidence of ES did not differ significantly between melphalan formulations. Future research is needed to determine whether the faster time to engraftment seen with PG-free melphalan may translate to a decrease in LOS. [ABSTRACT FROM AUTHOR]

Targeted cancer therapy is rapidly evolving the landscape of personalized health care. Novel approaches to selectively impeding tumour growth carry significant potential to improve survival outcomes, particularly for reproductive-aged patients harbouring treatment refractory disease. Current agents fall within two classes: immunotherapy and small molecule inhibitors. These are collectively divided into the following subclasses: monoclonal antibodies; immunomodulators; adoptive cell therapy; treatment vaccines; kinase inhibitors; proteasome inhibitors; metalloproteinase and heat shock protein inhibitors; and promoters of apoptosis. The short- and long-term effects of these treatments on the female reproductive system are not well understood. As a result, clinicians are rendered unable to appropriately counsel women on downstream effects to their fertility. Data-driven consensus recommendations are desperately needed. This review aims to characterize the effect of targeted cancer therapy on the female hypothalamic–pituitary–ovary axis, direct ovarian function and conception. [ABSTRACT FROM AUTHOR]

Aim: This systematic review identifies, appraises and synthesizes the evidence on the provision of fundamental nursing care to hospitalized patients with a highly infectious virus and the effectiveness of adaptations to overcome barriers to care. Design: Systematic review. Data Sources: In July 2020, we searched Medline, PsycINFO (OvidSP), CINAHL (EBSCOhost), BNI (ProQuest), WHO COVID‐19 Database (https://search.bvsalud.org/) MedRxiv (https://www.medrxiv.org/), bioRxiv (https://www.biorxiv.org/) and also Google Scholar, TRIP database and NICE Evidence, forwards citation searching and reference checking of included papers, from 2016 onwards. Review Methods: We included quantitative and qualitative research reporting (i) the views, perceptions and experiences of patients who have received fundamental nursing care whilst in hospital with COVID‐19, MERS, SARS, H1N1 or EVD or (ii) the views, perceptions and experiences of professional nurses and non‐professionally registered care workers who have provided that care. We included review articles, commentaries, protocols and guidance documents. One reviewer performed data extraction and quality appraisal and was checked by another person. Results: Of 3086 references, we included 64 articles; 19 empirical research and 45 review articles, commentaries, protocols and guidance documents spanning five pandemics. Four main themes (and 11 sub‐themes) were identified. Barriers to delivering fundamental care were wearing personal protective equipment, adequate staffing, infection control procedures and emotional challenges of care. These barriers were addressed by multiple adaptations to communication, organization of care, staff support and leadership. Conclusion: To prepare for continuation of the COVID‐19 pandemic and future pandemics, evaluative studies of adaptations to fundamental healthcare delivery must be prioritized to enable evidence‐based care to be provided in future. Impact: Our review identifies the barriers nurses experience in providing fundamental care during a pandemic, highlights potential adaptations that address barriers and ensure positive healthcare experiences and draws attention to the need for evaluative research on fundamental care practices during pandemics. [ABSTRACT FROM AUTHOR]

Young children with cleft palate with or without cleft lip (CL/P) are at risk for early vocabulary and speech sound production delays. Early intervention studies have shown some promising findings to promote early speech and vocabulary development following palate repair; however, we know little about how these interventions can be used in other international contexts. This study adapted an early speech and language intervention developed in the US, Enhanced Milieu Teaching with Phonological Emphasis (EMT+PE), to the Brazilian context at the Hospital for Rehabilitation of Craniofacial Anomalies at the University of São Paulo-Bauru. The purpose of this study was to compare the speech and language performance of 24 toddlers with CL/P randomized into an EMT+PE intervention group and a business-as–usual (BAU) comparison group over three time points: prior to, immediately following, and three months after intervention. Results immediately following intervention indicate gains in multiple measures of language. Three months following intervention, participants showed gains in both language and speech measures. [ABSTRACT FROM AUTHOR]

Objective: To describe our institution's experience with the AngioVac system.Background: Intracardiac and intravascular masses previously required surgical excision, but now, there are a number of minimally invasive options. With the advent of vacuum aspiration, more specifically the AngioVac System (AngioDynamics, NY, USA), there exists a system with both low mortality and minor complications. However, the number of retrospective studies remains limited. Outcome data for high-risk patients are also limited.Methods: Data were collected and analyzed in patients who underwent AngioVac therapy at our tertiary care center from January 2014 to December 2020.Results: Our results demonstrated a 93.3% intraoperative success rate and a 100% intraoperative survival rate. However, a number of complications, including but not limited to hematomas, anemia, and hypotension, occurred, as described below.Conclusions: Our experiences demonstrated good outcomes and continue to support the usefulness of the AngioVac System. The data also support the use of AngioVac as a treatment option for the debulking or removal of right heart masses in critically ill patients. [ABSTRACT FROM AUTHOR]

Patients with cancer are at increased risk of myocardial infarction (MI) and stroke. Guidelines do not address lipid profile targets for these patients. Within the lipid profiles, we hypothesized that patients with cancer develop MI or stroke at lower low density lipoprotein cholesterol (LDL-C) concentrations than patients without cancer and suffer worse outcomes. We linked nationwide longitudinal MI, stroke and cancer registries from years 2007–2017. We identified 42,148 eligible patients with MI (2421 prior cancer; 39,727 no cancer) and 43,888 eligible patients with stroke (3152 prior cancer; 40,738 no cancer). Median LDL-C concentration was lower in the prior cancer group than the no cancer group at incident MI [2.43 versus 3.10 mmol/L, adjusted ratio 0.87 (95% CI 0.85–0.89)] and stroke [2.81 versus 3.22 mmol/L, adjusted ratio 0.93, 95% CI 0.91–0.95)]. Similarly, median triglyceride and total cholesterol concentrations were lower in the prior cancer group, with no difference in high density lipoprotein cholesterol. Prior cancer was associated with higher post-MI mortality [adjusted hazard ratio (HR) 1.48, 95% CI 1.37–1.59] and post-stroke mortality (adjusted HR 1.95, 95% CI 1.52–2.52). Despite lower LDL-C concentrations, patients with prior cancer had worse post-MI and stroke mortality than patients without cancer. [ABSTRACT FROM AUTHOR]

Background Overuse of lumbar imaging is common in the emergency department (ED). Few trials have examined interventions to address this. We evaluated the effectiveness of a multifaceted intervention to implement guideline recommendations for low back pain in the emergency department. Methods We conducted a stepped-wedge, cluster- randomised trial in four EDs in New South Wales, Australia. After a 13-month control phase of usual care, the EDs received a multifaceted intervention to support guideline- endorsed care in a random order, based on a computer-generated random sequence, every 4 weeks over a 4- month period. All sites were followed up for at least 3 months. The primary outcome was the proportion of low back pain presentations receiving lumbar imaging. Secondary healthcare utilisation outcomes included prescriptions of opioid and non- opioid pain medicines, inpatient admissions, length of ED stay, specialist referrals and re- presentations. Clinician beliefs and knowledge about low back pain care were measured before and after the intervention. Patient-reported pain, disability, quality of life and satisfaction were measured at 1, 2 and 4 weeks post ED presentation. Results A total of 269 ED clinicians and 4625 episodes of care for low back pain (4491 patients) were included. The data did not provide clear evidence that the intervention reduced lumbar imaging (OR 0.77; 95% CI 0.47 to 1.26; p=0.29). It did reduce opioid use (OR 0.57; 95% CI 0.38 to 0.85; p=0.006) and improved clinicians' beliefs (mean difference (MD), 2.85; 95% CI 1.85 to 3.85; p<0.001; on a scale from 9 to 45) and knowledge about low back pain care (MD, 0.48; 95% CI 0.13 to 0.83; p<0.01; on a scale from 0 to 11). There was no difference in pain scores at 1-week follow-up (MD, 0.04; 95% CI -1.00 to 1.08; p=0.94; on a scale from 0 to 10). A similar trend was observed for all other patient- reported outcomes and time points. This study found no effect on the other secondary healthcare utilisation outcomes. Conclusion It is uncertain if a multifaceted intervention to implement guideline recommendations for low back pain care decreased lumbar imaging in the ED; however, it did reduce opioid prescriptions without adversely affecting patient outcomes. [ABSTRACT FROM AUTHOR]

The aim of the current cross-sectional study was to examine the effects of specific anxiety sensitivity (AS) dimensions (AS -Physical, -Cognitive, and -Social concerns) on exercise tolerance (i.e. 6-minute walk test) and factors that interfere with cardiopulmonary rehabilitation (CPR) and exercise adherence (i.e. depression and anxiety symptoms) among individuals seeking treatment in cardiopulmonary rehabilitation (CPR). Participants were 69 individuals (65.2% male, Mage = 63.60, SD = 12.55, Range = 27–85 years) with various cardiovascular or pulmonary conditions meeting criteria for CPR entry, who presented for an intake appointment at an outpatient phase 2 CPR clinic. Higher levels of AS-Physical and-Social concerns were significantly associated with poorer exercise tolerance and greater generalized anxiety symptoms, respectively. Though none of the AS dimensions were significant individual predictors, they were collectively associated with greater depressive symptoms. Future work should assess whether it may be useful to target AS in some patients prior to or throughout CPR. [ABSTRACT FROM AUTHOR]

Background Lenvatinib + pembrolizumab is approved for the first-line treatment of advanced renal cell carcinoma (RCC). In the CLEAR trial, the combination showed statistically significant/clinically meaningful improvements in overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) vs sunitinib (Motzer R et al. NEJM. 2021). As immune checkpoint inhibitors (ICIs) have become standards of care as first-line treatment of RCC, an unmet need exists for patients who have disease progression after treatment with ICIs. A phase 1b/2 trial of lenvatinib + pembrolizumab was performed in multiple tumor types enrolling patients who had or had not received prior therapy; the primary analysis of the RCC cohort has been reported previously (Lee C-H et al. Lancet Oncol. 2021). Here, we report the final results of this RCC cohort with an additional 24 months of follow-up. Methods Eligible patients ≥18 years old with measurable disease were treated with lenvatinib 20 mg daily + pembrolizumab 200 mg once every 3 weeks. The primary endpoint (ORR at week 24 [ORRwk24] per immune-related [ir] RECIST by the investigators) has been previously reported (Lee C-H et al. Lancet Oncol. 2021). Secondary endpoints included ORR, duration of response (DOR), PFS (each by the investigators), OS and safety. In the analyses reported herein, efficacy data were grouped by prior therapy patients had received, including ICI-pretreated, treatment-naïve, and previously treated but ICI-naïve. Tumors were assessed by the investigators per irRECIST and RECIST v1.1 (modified to allow assessment of ≤10 target lesions [≤5 per organ]). Results 145 Patients were enrolled, of whom 105 were ICI-pretreated, 23 were treatment-naïve, and 17 were previously treated ICI-naïve. By the final database lock date (August 24, 2022), the median duration of follow-up for OS was 37.7 months (95% CI 35.2–42.7). Efficacy analyses included 104 ICI-pretreated patients and 22 treatment-naïve patients; 1 patient in either group was excluded as they were negative for clear cell disease. Per irRECIST by investigator assessment, ORR was 62.5% for ICI-pretreated patients (median DOR: 14.1 months), 77.3% for treatment-naïve patients (median DOR: 24.2 months), and 52.9% for previously treated ICI-naïve patients (median DOR: 9.0 months) (Table). Notably, 18-month PFS rates were 38.0% for ICI-pretreated patients, 70.5% for treatment-naïve patients, and 36.1% for previously treated ICI-naïve patients (Table). The median OS was 32.1 months for ICI-pretreated patients, 55.8 months for treatment-naïve patients, and 30.3 months for previously treated ICI-naïve patients; 24-month OS rates were >50% in all groups. Additional efficacy data are included in the Table. For those who had their dose of lenvatinib reduced (per recommended algorithms for standard adverse event [AE] management) the median time to first dose reduction was 2.10 months (range 0.1–16.6) for ICI-pretreated patients (n=75), 6.47 months (range 0.3–33.1) for treatment-naïve patients (n=18), and 2.89 months (range 1.0–12.5) for previously treated ICI-naïve patients (n=10). Overall, treatment-related (TR) AEs were reported in 99.3% of all 145 patients; grade ≥3 TRAEs were reported in 66.2%. The most common TRAE was diarrhea (n=88). Treatment-emergent, clinically significant (CS) AEs and AEs of special interest for pembrolizumab (AEOSIs) were reported in 95.2% and 55.9% of patients, respectively. Hypertension was the most common grade ≥3 CSAE (n=37), severe skin reactions were the most common grade ≥3 AEOSI (n=6). The median time to first onset of CSAEs was 0.64 months; the median time to first onset of AEOSIs was 2.07 months. Conclusions Lenvatinib + pembrolizumab demonstrated promising and durable antitumor activity with a manageable safety profile in patients with metastatic RCC, including in those who were ICI-pretreated. To our knowledge, this represents the largest cohort of ICI-pretreated patients with RCC prospectively treated in a clinical trial. CDMRP DOD Funding: no [ABSTRACT FROM AUTHOR]

Evidence shows stereotactic ablative body radiotherapy (SABR) is used as a non-invasive ablative therapy in the treatment of multisite oligometastatic (OM) and oligoprogressive (OP) diseases originating from metastatic breast cancer. This study aims to report the treatment outcomes and to investigate what factors that are prognostic in terms of local control, progression-free survival (PFS) and overall survival (OS) in patients receiving SABR for extracranial OM and OP diseases originating from metastatic breast cancer. A retrospective review on treatment records of patients with OM and OP from metastatic breast cancer who underwent SABR at a single was carried out. SABR was performed with daily image-guided radiotherapy (IGRT) using a dedicated robotic SABR machine. Local control, PFS and OS were calculated using Kaplan-Meier statistics and the post-treatment toxicity data was scored following the CTCAE v4.0 protocol. Univariate and multivariate Cox regression tests were used in the subgroup analysis of prognostic factors on PFS and OS including patients' age, types of follow-up imaging (staging CT only vs whole-body MR/PET), metastases status (OM vs OP), primary breast cancer tumour grade, hormone receptors (ER/PR/HER2) status, change of systemic treatments at SABR, number of metastases, SABR treatment sites and doses. 56 metastatic breast cancer patients (38 patients with OM and 18 patients with OP) were involved in this retrospective review. The median follow-up was 35.6 months (range 4.0–132.9 months). The estimated local control at 1 , 2 and 5 years were 90.9%, 88.7% and 88.7%, respectively. The estimated median PFS was 19.2 months (95%CI 10.3–28.1 months); the PFS at 1, 2 and 5 years were 63.3%, 44.4% and 33.2%. The estimated OS at 1, 2 and 5 years were 98.0%, 91.9% and 74.3%, respectively with the estimated median OS of 105.1 months (95%CI 51.5–158.7 months). The vast majority of patients tolerated the treatment well with the commonest acute side effects as grade 1 fatigue. There were no statistically significant factors found in OS regression analysis. The types of follow-up imaging, metastases status, oestrogen receptor status, and number of metastases for SABR were statistically significant factors (p < 0.05) in the multivariate Cox regression analysis on PFS. There are limited studies published on the efficacy and post-treatment toxicities of metastatic breast cancer OM and OP SABR with adequate length of follow-up. This study confirmed that SABR was a safe, non-invasive treatment option for patients with extracranial OM and OP diseases originated from primary breast cancer in terms of the acceptable post-treatment toxicities. • This study reported SABR treatment outcomes for multisite OM and OP diseases originating from metastatic breast cancer • It showed modest local control and post-treatment toxicities on the SABR of extracranial OM and OP from metastatic breast cancer. • The types of follow-up imaging, OM vs OP, oestrogen receptor status, and number of metastases for SABR can be used as PFS prognostic factors. [ABSTRACT FROM AUTHOR]

Introduction/Purpose: Uncertainty exists regarding the best treatment for acute Achilles tendon ruptures. Simultaneous comparison of the multiple treatment options using traditional study designs is problematic; multiarm clinical trials often are logistically constrained to small sample sizes, and traditional meta-analyses are limited to comparisons of only two treatments that have been compared in head-to-head trials. Network meta-analyses allow for simultaneous comparison of all existing treatments utilizing both direct and indirect evidence. We performed a network meta-analysis of randomized controlled trials to answer the following questions: Considering open repair, minimally invasive surgery repair, functional rehabilitation, or primary immobilization for acute Achilles tendon ruptures, (1) which intervention is associated with the lowest risk of rerupture? (2) Which intervention is associated with the lowest risk of complications resulting in surgery? Methods: Five databases and grey literature sources were searched from inception to September 30, 2019. Included studies were RCTs comparing treatment of acute Achilles tendon ruptures using two or more of the following interventions: primary immobilization, functional rehabilitation, open surgical repair, or MIS repair. We excluded studies enrolling patients with chronic ruptures, reruptures, and preexisting Achilles tendinopathy as well as studies with more than 20% loss to follow-up or less than 6 months of follow-up. Nineteen RCTs (1316 patients) were included in the final analysis. The mean number of patients per study treatment arm was 35 +- 16, mean age was 41 +- 5 years, mean sex composition was 80% +- 10% males, and mean follow-up was 22 +- 12 months. The four treatment groups were compared for the main outcomes of rerupture and complications resulting in operation. The analysis was conducted using random-effects Bayesian network meta-analysis with vague priors. Results: Treatment with primary immobilization had a greater risk of rerupture than open surgery (odds ratio 4.06 [95% credible interval {CrI} 1.47 to 11.88]; p < 0.05). There were no other differences between treatments for risk of rerupture. Minimally invasive surgery was ranked first for fewest complications resulting in surgery and was associated with a lower risk of complications resulting in surgery than functional rehabilitation (OR 0.16 [95% CrI 0.02 to 0.90]; p < 0.05), open surgery (OR 0.22 [95% CrI 0.04 to 0.93]; p < 0.05), and primary immobilization (OR < 0.01 [95% CrI < 0.01 to 0.01]; p < 0.05). Risk of complications resulting in surgery was no different between primary immobilization and open surgery (OR 1.46 [95% CrI 0.35 to 5.36]). Data for patient-reported outcome scores and return to activity were inappropriate for pooling secondary to considerable clinical heterogeneity and imprecision associated with small sample sizes. Conclusion: Faced with acute Achilles tendon rupture, patients should be counseled that the risk of rerupture likely is no different across contemporary treatments. Considering the possibly lower risk of complications resulting in surgery associated with MIS repair, patients and surgeons must balance any benefit with the potential risks of MIS techniques. As treatments continue to evolve, consistent reporting of validated patient-reported outcome measures is critically important to facilitate analysis with existing RCT evidence. Infrequent but serious complications such as rerupture and deep infection should be further explored to determine whether meaningful differences exist in specific patient populations. [ABSTRACT FROM AUTHOR]

Expandable transforaminal lumbar interbody fusion (TLIF) cages capable of multidirectional in situ expansion have gained popularity as they increase axial surface area for fusion and may enhance lordotic correction through a traditional minimally invasive surgery (MIS) surgical corridor. We evaluated and compared the radiographic and clinical outcomes between a novel expandable versus static minimally invasive surgery TLIF cage for the treatment of degenerative disk disease. A single-center retrospective review of 120 consecutive adult patients undergoing 1- or 2-level MIS TLIF with an expandable (n = 60) or static cage was performed between 2015 and 2019. Preoperative and 1-year postoperative radiographic and clinical outcomes were assessed by upright flexion/extension radiographs and serial confidential surveys. One-hundred twenty patients (mean age 63.5 years, 60.0% female) undergoing 1- and 2-level MIS TLIF met inclusion criteria. A statistically significant reduction of spondylolisthesis, restoration of foraminal height as well as anterior and posterior disk height was achieved in both cohorts, however was greater in the expandable cage cohort (ECC) (all P < 0.05). Comparable rates of fusion, 93% and 91%, were observed in the ECC and static cage cohort. A significant reduction in Numeric Pain Rating Scale back and Oswestry Disability Index scores were observed in both cohorts but were more pronounced in the ECC (5.9 ± 2.4 to 2.2 ± 1.9 and 37.3 ± 16.2 to 17.1 ± 15.2) versus static cage cohort (6.2 ± 2.8 to 3.2 ± 2.5 and 41.8 ± 16.1 to 24.3 ± 17.5) (P < 0.05). One instance of cage migration requiring reoperation occurred in the ECC. Taken together, these radiographic and clinical findings suggest an expandable cage placed through an MIS corridor represents a safe, equitable, and efficacious alternative to a static TLIF in adults with degenerative lumbar pathology. [ABSTRACT FROM AUTHOR]

Bulevirtide (BLV) is a HDV/HBV entry inhibitor that is associated with virologic response (responders, HDV-RNA undetectable or ≥2 log 10 IU/ml decrease from baseline) in >50% of patients after a 24-week treatment. However, some patients only achieve a <1 log 10 IU/ml decline in HDV-RNA after the 24-week treatment (non-responders). Here, we report a viral resistance analysis in participants receiving BLV monotherapy who were non-responders or experienced virologic breakthrough (VB, i.e., two consecutive increases in HDV-RNA of ≥1 log 10 IU/ml from nadir or two consecutive HDV-RNA detectable results if previously undetectable) from the phase II MYR202 and phase III MYR301 study. Deep-sequencing of the BLV-corresponding region in HBV PreS1 and of the HDV HDAg gene, as well as in vitro phenotypic testing, were performed for the participant with VB (n = 1) and non-responders (n = 20) at baseline (BL) and Week 24 (WK24). No amino acid exchanges associated with reduced susceptibility to BLV within the BLV-corresponding region or within HDAg were identified in isolates from any of the 21 participants at BL or at WK24. Although variants (HBV n = 1; HDV n = 13) were detected at BL in some non-responders or in the participant with VB, none were associated with reduced sensitivity to BLV in vitro. Furthermore, the same variant was detected in virologic responders. A comprehensive phenotypic analysis demonstrated that the BLV EC 50 values from 116 BL samples were similar across non-responders, partial responders (HDV RNA decline ≥1 but <2 log 10 IU/ml), and responders regardless of the presence of HBV and/or HDV polymorphisms. No amino acid substitutions associated with reduced sensitivity to BLV monotherapy were detected at BL or WK24 in non-responders or the participant with VB after 24-week BLV treatment. This is the first study investigating the development of resistance in patients treated with BLV. Excluding resistance to BLV as an explanation for an insufficient decrease in HDV-RNA levels during BLV therapy is an important finding for patients, clinicians, and researchers. It demonstrates that BLV has a high barrier to resistance, indicating it is safe and suitable for long-term treatment, although long-term surveillance for resistance should be performed. Our results hint at other still unknown mechanisms as an explanation for the persistence of serum HDV-RNA during inhibition of viral entry. NCT03546621 and NCT03852719. [Display omitted] • Baseline variants in HBsAg, HDAg, or NTCP are not associated with treatment outcome. • Treatment-emergent variants are rare and not associated with bulevirtide resistance. • Clinical isolates from non-responders are sensitive to bulevirtide in vitro. [ABSTRACT FROM AUTHOR]

Aims: Complete mesocolic excision (CME) has been proposed as a way to improve the oncological outcomes in patients with colon cancer. To investigate whether there is rationale for adopting the technique in Scotland, our aim was to define the incidence of disease recurrence following standard right hemicolectomy and to compare this with published CME outcomes.Methods: Data was collected on consecutive patients undergoing right or extended right hemicolectomy for colonic adenocarcinoma (2012-2017) at three hospitals in Scotland (Raigmore Hospital, Aberdeen Royal Infirmary and Glasgow Royal Infirmary). Emergency or palliative surgery was excluded. Patients were followed up with CT scans and colonoscopy for a minimum of 3 years.Results: 689 patients (M 340, F 349) were included. 30-day mortality was 1.6%. Final pathological stage was Stage I (14%), Stage II (49.8%) and Stage III (36.1%). During follow-up, 10.5% developed loco-regional recurrence and 12.2% developed distant metastases. The 1, 3 and 5-year disease-free survival (DFS) was 94%, 84% and 82% respectively. Primary determinants of recurrence were T stage (p < 0.001), N stage (p < 0.001), apical node involvement (p < 0.001) and EMVI (p < 0.001). When compared to the literature, 30-day mortality was lower than many published series and DFS rates were similar to the largest CME study to date (4 year DFS 85.8% versus 83%).Conclusion: The outcomes of patients undergoing right hemicolectomy in Scotland compare favourably with many published CME studies. The technique demands further evaluation before it can be recommended for adoption into routine surgical practice. [ABSTRACT FROM AUTHOR]

Abstract: Chronic neuropathic pain (NP) is a common and often debilitating secondary condition for persons with spinal cord injury (SCI) and is minimally responsive to existing pharmacological and nonpharmacological treatments. The current preliminary investigation describes the feasibility and initial comparative efficacy of an interactive virtual reality walking intervention, which is a novel extension of visual feedback/illusory walking therapies shown to reduce SCI NP. Virtual reality walking intervention builds on previous research by, for the first time, allowing individuals with SCI NP to volitionally control virtual gait to interact with a fully immersive virtual environment. The current pilot study compared this interactive, virtual walking intervention to a passive, noninteractive virtual walking condition (analogous to previous illusory walking interventions) in 27 individuals with complete paraplegia (interactive condition, n = 17; passive condition, n = 10; nonrandomized design). The intervention was delivered over 2 weeks in individuals' homes. Participants in the interactive condition endorsed significantly greater reductions in NP intensity and NP-related activity interference preintervention to postintervention. Notable improvements in mood and affect were also observed both within individual sessions and in response to the full intervention. These results, although preliminary, highlight the potentially potent effects of an interactive virtual walking intervention for SCI NP. The current study results require replication in a larger, randomized clinical trial and may form a valuable basis for future inquiry regarding the mechanisms and clinical applications of virtual walking therapies. [ABSTRACT FROM AUTHOR]

Background Context: Postoperative pain control following posterior lumbar fusion continues to be challenging and often requires high doses of opioids for pain relief. The use of ketorolac in spinal fusion is limited due to the risk of pseudarthrosis. However, recent literature suggests it may not affect fusion rates with short-term use and low doses.Purpose: We sought to demonstrate noninferiority regarding fusion rates in patients who received ketorolac after undergoing minimally invasive (MIS) posterior lumbar interbody fusion. Additionally, we sought to demonstrate ketorolac's opioid-sparing effect on analgesia in the immediate postoperative period.Study Design/setting: This is a prospective, randomized, double-blinded, placebo-controlled trial. We are reporting our interim analysis.Patient Sample: Adults with degenerative spinal conditions eligible to undergo a one to three-level MIS transforaminal lumbar interbody fusion (TLIF).Outcome Measures: Six-month and 1-year radiographic fusion as determined by Suk criteria, postoperative opioid consumption as measured by intravenous milligram morphine equivalent, length of stay, and drug-related complications. Self-reported and functional measures include validated visual analog scale, short-form 12, and Oswestry Disability Index.Methods: A double-blinded, randomized placebo-controlled, noninferiority trial of patients undergoing 1- to 3-level MIS TLIF was performed with bone morphogenetic protein (BMP). Patients were randomized to receive a 48-hour scheduled treatment of either intravenous ketorolac (15 mg every 6 hours) or saline in addition to a standardized pain regimen. The primary outcome was fusion. Secondary outcomes included 48-hour and total postoperative opioid use demonstrated as milligram morphine equivalence, pain scores, length of stay (LOS), and quality-of-life outcomes. Univariate analyses were performed. The present study provides results from a planned interim analysis.Results: Two hundred and forty-six patients were analyzed per protocol. Patient characteristics were comparable between the groups. There was no significant difference in 1-year fusion rates between the two treatments (p=.53). The difference in proportion of solid fusion between the ketorolac and placebo groups did not reach inferiority (p=.072, 95% confidence interval, -.07 to .21). There was a significant reduction in total/48-hour mean opioid consumption (p<.001) and LOS (p=.001) for the ketorolac group while demonstrating equivalent mean pain scores in 48 hours postoperative (p=.20). There was no significant difference in rates of perioperative complications.Conclusions: Short-term use of low-dose ketorolac in patients who have undergone MIS TLIF with BMP demonstrated noninferior fusion rates. Ketorolac safely demonstrated a significant reduction in postoperative opioid use and LOS while maintaining equivalent postoperative pain control. [ABSTRACT FROM AUTHOR]